A structured DAG enriched mustard oil system ameliorates hypercholesterolemia through modulation of AMPK and NF-κB signaling system

[Display omitted] •Diacylglycerol-enriched mustard oil evinces anti-hypercholesterolemic activity.•Therapeutic benefits of DAG-MO have been illustrated by molecular profiling studies.•DAG-MO showed better in vivo absorption characteristics.•DAG-MO normalizes hypercholesterolemic pro-inflammatory cytokine profile.•DAG-MO activates AMPK-α signaling pathway to counter oxidative-stress manifestations. Sometimes few dietary formulations can play a nutritional as well as therapeutical effect on the human body and those formulations can be termed as nutraceuticals. Triacylglycerols can be re-engineered and formulated as a diacylglycerol (DAG) system with enhanced absorption and more potent nutraceutical profile. The present study aimed to develop a DAG enriched mustard oil (DAG-MO) dietary formulation to treat preclinical conditions of hypercholesterolemia and exploring its underlying mode of action.The DAG-MO was produced by an established technique of chemical esterification, purification, and was diet supplemented to treat pre-clinical conditions of hypercholesterolemia as per RDA guidelines. Investigative biochemical, molecular, flow-cytometric, confocal laser scanning micrography etc. were performed towards data acquisition and relevant data interpretation. The results demonstrated that co-administration with DAG-MO significantly reduced the Hypercholesterolemic diet (HCD)-induced hypercholesterolemia, associated hyperglycemia and metabolic syndrome as observed from the reduction in serum glucose and hepatic triglyceride accumulation along with the suppression of total cholesterol level. DAG-MO markedly suppressed HCD-induced hepatic inflammation by the downregulation of p38-MAPK/NF-κB-guided proinflammatory cytokine burden.Also, hypercholesterolemia-associated hepatic steatosis and lipogenesis were also inhibited by the modulation of AMPK-regulated suppression of PPAR-γ, SREBP1c, and ACC. The study provides empirical evidences to support the importance of diet-supplementation of the engineered DAG-MO in treating manifestations of metabolic syndrome.